Expression of Pyruvate Kinase M2 in Human Bladder Cancer and Its Correlation with Clinical Parameters and Prognosis

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2018 Apr 27

PMID 29695915

Citations 17

Authors

Changkun Huang

Zhichao Huang

Peiming Bai

Guangcheng Luo

Xiaokun Zhao

Xinjun Wang

Affiliations

Soon will be listed here.

Abstract

Background: Pyruvate kinase M2 (PKM2) is a key regulator of the Warburg effect and has critical functions in glycolysis, contributing to the Warburg effect, tumor growth, angiogenesis, cell division, metastasis, and apoptosis. The high expression of PKM2 in various solid tumors renders it a potential biomarker of tumorigenesis and tumor invasion, but the expression and role of PKM2 in bladder cancer have not been studied extensively.

Patients And Methods: Western blot and immunohistochemistry (IHC) were used to measure the expression of PKM2, and quantitative real-time polymerase chain reaction (PCR) was performed to determine PKM2 mRNA levels. The relationships between PKM2 expression and clinicopathological parameters and prognosis were analyzed using the Kaplan-Meier plots and a Cox proportional hazards regression model.

Results: Compared with paired adjacent normal bladder tissues, PKM2 mRNA and protein levels were found to be higher in urothelial carcinoma of the bladder (UCB) samples by real-time PCR and Western blot. By IHC, high expression of PKM2 was seen in 117 of 215 UCBs (54.4%) and in eight of 90 adjacent normal bladder tissues (8.9%). The expression of PKM2 was significantly associated with grade, stage, and lymph node status (<0.001). In the univariate survival analysis, a significant association between PKM2 expression and shorter patient survival was observed (<0.001). In different subsets of UCB patients, we found that PKM2 expression was a prognostic factor in patients with G2 (=0.009), G3 (<0.001), pTa/pTis (=0.006), pT1, pT2-4, and pN disease (<0.001). Importantly, PKM2 expression (=0.003), with tumor histological grade (<0.001), pT (<0.001), and pN status (=0.005), was a significant independent prognostic parameter in the multivariate analysis.

Conclusion: PKM2 protein and mRNA are upregulated in UCBs and may serve as molecular markers for a poor prognosis in patients with UCB.

Citing Articles

The regulatory roles and clinical significance of glycolysis in tumor.

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Cisplatin-Resistant Urothelial Bladder Cancer Cells Undergo Metabolic Reprogramming beyond the Warburg Effect.

Afonso J, Barbosa-Matos C, Silvestre R, Pereira-Vieira J, Goncalves S, Mendes-Alves C Cancers (Basel). 2024; 16(7).

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[RBMX overexpression inhibits proliferation, migration, invasion and glycolysis of human bladder cancer cells by downregulating PKM2].

Yan Q, Zeng P, Huang S, Tan C, Zhou X, Qiao J Nan Fang Yi Ke Da Xue Xue Bao. 2024; 44(1):9-16.

PMID: 38293971 PMC: 10878900. DOI: 10.12122/j.issn.1673-4254.2024.01.02.

Pyruvate kinase M2 (PKM-2) expression and prognostic significance in glioblastoma patients.

Yavuz B, Kilinc F, Kanyilmaz G, Aktan M J Neurooncol. 2023; 165(3):527-533.

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Expression of substance P, neurokinin 1 receptor, Ki-67 and pyruvate kinase M2 in hormone receptor negative breast cancer and evaluation of impact on overall survival.

Al-Keilani M, Bdeir R, Elstaty R, Alqudah M BMC Cancer. 2023; 23(1):158.

PMID: 36797689 PMC: 9936699. DOI: 10.1186/s12885-023-10633-8.

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